B lymphocytes express antigen specific membrane immunoglobulins [mIg] on their surface. Engagement of mIg and interaction with helper T cells stimulates B cells to undergo an ordered process of signal transduction leading to cell growth and antibody production. Receptor crosslinking by anti-Ig initiates several immediate responses including, the mobilization of calcium, the breakdown of polyphosphoinositides and the activation of protein kinase C. Endocytosis of occupied MIg allows the internalization of antigen and its subsequent processing and NHC restricted presentation to T cells. MIg has only a short cytoplasmic tail suggesting that it is not sufficient to mediate signal transduction. However, MIg associates with at least two other membrane proteins, Ig-alpha and Ig-beta, to form a B cell receptor complex [BCR]. Tyrosine phosphorylation is one of the earliest signaling events, in B cell activation induced by ligation of the mlg receptor. This includes the induction of phosphorylation and enhanced kinase activity as well as association of a novel protein tyrosine kinase, PTK72/syk, and several src- related tyrosine kinases including lyn, blk, fyn and 1ck. We demonstrated that tyrosine kinase inhibitors block the internalization of MIg-ligand complexes following receptor crosslinking. Furthermore, Takagi and co- workers reported the concentration of tyrosine phosphorylated proteins associated with the plasma membrane under MIg receptors modulated by anti- Ig. Based on these observations we propose to test our hypothesis that tyrosine phosphorylation is an important mediator of ligand induced internalization of MIg, possibly by mediating the induced association of the receptor complex with the cytoskeleton. This will entail cloning human and murine syk, establishing localization of MIg, tyrosine kinases and components of the cytoskeleton and a molecular genetic analysis to define the role of the tyrosine kinases in MIg mediated B cell activation and internalization.